Laboratory studies in biochemical pharmacology, cell cultures, and preclinical projects have been planned in conjunction with the clinical studies (serial number 3024), thereby ensuring an integrated research program in the Medical Oncology Branch. The Oncologic Pharmacology Unit conducts investigations primarily of new anticancer agents but also carries out some studies of established agents. It is responsible for the Phase I testing of new agents in the Branch and for conducting clinical pharmacology and biochemical pharmacology studies. In addition, because we feel that the value of clinical pharmacology studies is often lost through inadequate interpretation of the data generated, we have devoted a considerable effort to developing pharmacokinetic modelling of anticancer drugs using the extensive computer facilities of NIH. The work started with single dose ifosfamide has been continued with daily x 3 ifosfamide without, however, altering the nature of the dose limiting toxicity as had been hoped. Studies on thalicarpine were completed; an MTD for single dose and weekly administration has been reported and pharmacology studies have shown a long body retention of the drug. A major effort has been made in the investigation of the pharmacology and pharmacokinetics of the epipodophyllotoxins VP16-213 and VM26. Interesting pharmacokinetic differences between the two drugs have been found and pharmacokinetic models are under development.